A known compound for producing an oral sensation of cold is menthol (2-isopropyl-5-methyl-cyclohexanol), which has been extensively applied as an additive in, for example, foodstuffs and oral hygiene products. It is used primarily because it elicits a sensation of coolness in the mouth, and because it has a pleasing mint flavour and odour. The cooling effect of menthol is due to the action of menthol on the nerve endings of the human body which detect hot and cold stimuli. In particular, menthol is believed to activate cold receptors on nerve endings. However, the use of menthol is limited by its strong minty smell and relative volatility.
To find alternative cooling compounds, many investigations have focused upon compounds which are menthol derivatives or analogues. Other cooling compounds have been based upon fundamentally different molecular species. A particularly well researched group of compounds comprises 1,4-disubstituted tetrahydropyrimidinone derivatives.
We have now found a class of tricyclic molecules which are substituted hydrobenzothienopyrimidines or analogues thereof and which have excellent cooling or refreshing properties.